The eyes have it: seeking expressions of the genetic risk for developing alcoholism

Prior research indicates that the brain’s response to alcohol is related
to a genetic risk for alcoholism.

New research examines high-velocity eye movements, called saccades, in
individuals with and without a family history of alcoholism.

Those with a family history of alcoholism have slightly but consistently
slower saccadic eye movement than those without a history, yet appear to “adapt”
more quickly to continued alcohol exposure.

Genetic factors play a key role in the development of alcoholism. A family
history of alcoholism does not, however, guarantee that individual offspring
will develop the disease. In an effort to discover identifying “markers”
of those at risk for alcoholism, researchers in the October issue of Alcoholism:
Clinical & Experimental Research evaluate the influence of a family
history of alcoholism on the response of saccadic eye movements to alcohol.

Saccades are high-velocity eye movements made from one point to another, as
in reading. Their main function is to bring the image of a target from the visual
periphery onto the fovea centralis (center of the retina), where vision is most
acute. The saccadic control system is sensitive to alcohol, and saccadic parameters
provide reliable measures of alcohol’s effects in a dose-dependent manner.

“The premise of our research is that the brain’s response to alcohol
is related to a genetically influenced risk for alcoholism,” said Sean
O’Connor, professor of psychiatry at Indiana University School of Medicine
and corresponding author for the study. “We used a familial history of
alcoholism as a proxy for genetic influence, since specific genes cannot yet
be identified. Saccadic eye-movements fulfilled all the criteria for a good
measure of the brain’s response to alcohol: they are known to be genetically
influenced; they are a very reliable measure of brain function as most people
will execute these movements in the same way day after day; they are quite sensitive
to alcohol; and a lot is known about the systems of neurons that control the
movements.” O’Connor explained that associating response of saccades
to alcohol with the genetic risk for alcoholism is the first step in seeking
specific genes increasing that risk.

Researchers evaluated saccadic performance in 54 adults (27 males, 27 females)
with a family history of alcoholism, and 49 adults (24 males, 25 females) without
a family history of alcoholism. Participants were given alcohol and a placebo
in a counter-balanced order. The alcohol was administered intravenously in order
to achieve a breath alcohol concentration of 60 mg% in 20 minutes and to maintain
it for 160 minutes. Saccadic eye movement was tested before each session (called
baseline), and twice during the maintained level of intoxication.

The two groups showed significant overall differences in operational characteristics
of the saccadic control system, both at baseline and when the brain was exposed
to alcohol. Subjects with a family history of alcoholism were slightly but consistently
slower than subjects without a history throughout the sessions, and appeared
to “recover” baseline measures despite prolonged and constant exposure
to alcohol.

“A key finding of our study is that the adaptive response of saccades
to alcohol is associated with a family-history status known to be associated
with a genetic influence on the risk for alcoholism,” said O’Connor.
In other words, brain function among those with a family history of alcoholism
returned towards “normal” despite continued exposure to alcohol.

“We are still trying to learn what is actually inherited that affects
the risk of alcoholism,” said David Crabb, professor of medicine and of
biochemistry and molecular biology at Indiana University School of Medicine.
“In other words, is the inherited risk related to brain control functions?
to the inability to control drinking? to the euphoria of drinking? We need to
know this in order to devise therapies that address the actions of alcohol on
the brain.” He called the study’s identification of brain functions
(the control of eye movement at a subconscious level) that are both influenced
by genetic factors (the family history of alcoholism) and show responses to
alcohol “an incremental yet important step toward understanding genetic
influences on alcohol’s effects on the brain.”

Crabb said these findings may one day have practical applications, such as
developing a battery of easy-to-use measures of risk. “We could test children
of alcoholics,” he said. “Perhaps combining the results of the eye
movement tests in young people with other measures would predict their risk
of alcoholism or other alcohol problems. If we could accurately tell people
if they are at a higher or lower risk of alcoholism based on their test results,
this could influence some people to reduce their drinking.”

O’Connor said it’s important for the field of alcohol research
to continue to examine the question: “What does alcohol have to do with
an increased risk for alcoholism?” His own research plans include quantifying
the degree to which genes influence responses to alcohol, examining how other
brain functions respond to alcohol, and expanding those studies to include experimental
control of how quickly alcohol reaches and leaves the brain.

Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.